Immunohistochemical detection of c-erbB-2 and p53 in benign breast disease and breast cancer risk

BACKGROUND: We studied the associations between c-erbB-2 protein overexpression and p53 protein accumulation in benign breast tissue and the risk of subsequent breast cancer. METHODS: We conducted a case-control study nested within the cohort of 4888 women in the National Breast Screening Study (NBSS) who were diagnosed with benign breast disease during active follow-up. Case subjects were the women who subsequently developed breast cancer (ductal carcinoma in situ [DCIS] or invasive carcinoma). Control subjects were matched to each case subject on NBSS study arm, screening center, year of birth, and age at diagnosis of benign breast disease. Histologic sections of benign and cancerous breast tissues were analyzed immunohistochemically. Information on potential confounding factors was obtained by use of a self-administered lifestyle questionnaire. RESULTS: Accumulation of p53 protein was associated with an increased risk of progression to breast cancer (adjusted odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.01-6.40), whereas c-erbB-2 protein overexpression was not (adjusted OR = 0.65; 95% CI = 0.27-1.53). The findings for c-erbB-2 and p53 did not differ among strata defined by menopausal status, allocation within the NBSS, history of breast disease, and whether the benign breast disease was detected at a scheduled screen or between screens. The results were also similar after exclusion of case subjects whose diagnosis of breast cancer occurred within 1 year of their diagnosis of benign breast disease and after exclusion of subjects with DCIS. CONCLUSIONS: p53 protein accumulation, but not c-erbB-2 protein overexpression, appears to be associated with an increased risk of progression to breast cancer in women with benign breast disease.     

Parity, age at first childbirth and the prognosis of primary breast cancer

Reproductive factors are known to be aetiologically important in breast cancer, but less is known regarding their effect on breast cancer prognosis. We have investigated the prognostic effect of age at first birth and total parity using data from the Danish Breast Cancer Cooperative Group that, since 1977, has collected population-based information on tumour characteristics, treatment regimes and follow-up status on Danish women with breast cancer. Details of pregnancy history were added from the Danish Civil Registration System and the National Birth Registry. Included in the study were 10,703 women with primary breast cancer. After adjusting for age and stage of disease (tumour size, axillary nodal status and histological grading), the number of full-term pregnancies was found without prognostic value. However, women with primary childbirth between 20 and 29 years experienced a significantly reduced risk of death compared with women with primary childbirth below the age of 20 years [20-24 years: relative risk (RR) = 0.88, 95% confidence interval (CI) 0.78-0.99; 25-29 years: RR = 0.80, 95% CI 0.70-0.91]. Further adjustment for oestrogen receptor status did not influence these results. The effect was not modified by age at diagnosis, tumour size or nodal status. In conclusion, low age at first childbirth, but not parity, was associated with a poor prognosis of breast cancer. We speculate whether women who develop breast cancer despite an early first full-term pregnancy might represent a selected group with a more malignant disease.     

Predictors of cancer progression in young adult men and women: Avoidance, intrusive thoughts, and psychological symptoms.

Psychological symptoms, avoidance, and intrusive thoughts were examined prospectively as predictors of cancer progression over a period of 1 year. Sixty-six male and female cancer patients who differed in their diagnoses and initial disease-severity ratings participated. Measures of psychological factors, disease severity, and type of treatment were obtained near time of diagnosis and disease status (no cancer, continued or recurrent cancer, or deceased) 1 year later. Cross-sectional analyses near the time of diagnosis showed that initial psychological variables were intercorrelated with one another but unrelated to initial disease prognosis. Longitudinal findings revealed that, after controlling for initial disease parameters and age, avoidance predicted disease status 1 year later; however, neither psychological symptoms nor intrusive thoughts and emotions accounted for additional variance in disease outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification and prediction of distress trajectories in the first year after a breast cancer diagnosis.

Objective: In this article, we aim to (a) identify distinct trajectories of psychological distress in the first year after a breast cancer diagnosis in women treated with adjuvant therapy and (b) explore possible predictors of these trajectories, that is, demographic, medical, and personal characteristics. Method: The 171 patients were assessed after diagnosis, after surgery, after adjuvant treatment, in the reentry phase, and in the (short-term) survivorship phase (2 and 6 months after the end of treatment, respectively). Main Outcome Measure: Psychological distress was assessed with the 12-item General Health Questionnaire. Results: There were four trajectories of distress: a group that experienced no distress (36.3%), a group that experienced distress only in the active treatment phase (33.3%), a group that experienced distress in the reentry and survivorship phase (15.2%), and a group that experienced chronic distress (15.2%). Personality and physical complaints resulting from adjuvant treatment could distinguish the distress trajectories. Mastery was the only unique predictor. Conclusion: Most patients were not distressed in response to breast cancer or only temporarily so. Yet, a minority of patients became or remained distressed after the end of treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radial scars in benign breast-biopsy specimens and the risk of breast cancer

BACKGROUND: Radial scars are benign breast lesions of uncertain clinical significance. In particular, it is not known whether these lesions alter the risk of breast cancer in women with benign breast disease. We conducted a case-control study of women who had benign breast lesions with or without radial scars. METHODS: We reviewed benign breast-biopsy specimens from 1396 women enrolled in the Nurses' Health Study, including 255 women in whom breast cancer subsequently developed and 1141 women without subsequent breast cancer (controls). The controls were matched to the women with subsequent breast cancer according to age and the year when the benign lesion was identified. The median follow-up after biopsy of the benign lesions was 12 years. RESULTS: Radial scars were identified in biopsy specimens from 99 women (7.1 percent). Most biopsy specimens with radial scars had only one radial scar (60.6 percent), and they tended to be incidental microscopical findings (median size, 4.0 mm). The women with radial scars had a risk of breast cancer that was almost twice the risk of the women without scars, regardless of the histologic type of benign breast disease (relative risk, 1.8; 95 percent confidence interval, 1.1 to 2.9). Among women who had proliferative disease without atypia as compared with women who had nonproliferative disease, the relative risk of breast cancer was 3.0 (95 percent confidence interval, 1.7 to 5.5) for those with radial scars and 1.5 (95 percent confidence interval, 1.1 to 2.1) for those without radial scars. Among women with atypical hyperplasia as compared with women with nonproliferative disease, the relative risk of breast cancer was 5.8 (95 percent confidence interval, 2.7 to 12.7) for those with radial scars and 3.8 (95 percent confidence interval, 2.4 to 5.9) for those without radial scars. CONCLUSIONS: Radial scars are an independent histologic risk factor for breast cancer.     

The impact of a psychological intervention on quality of life in non-metastatic breast cancer

The aim of this study was to determine whether psychological intervention had a beneficial effect on the quality of life and behaviour of women diagnosed with breast cancer. 36 consecutive patients with non-metastatic breast cancer assigned to surgery and systemic chemotherapy were randomised to receive either psychological intervention (weekly cognitive individual psychotherapy and bimonthly family counselling) or standard follow-up. Personality (16-PF and IIQ), quality of life (FLIC), and depression (BDI) scores were the endpoints for this study, and the questionnaires were completed by the patients at diagnosis, and up to 9 months after diagnosis. Cognitive psychotherapy and family counselling improved both depression and quality of life indexes compared with the control group. Better emotional coping behaviours were also revealed by some changes in personality traits in the intervention group.     

Possible mechanisms by which alcohol may influence the development of oral cancer--a review

Hepatitis C virus (HCV) infection is one of the major causes leading to orthotopic liver transplantation (OLT) worldwide. Although viral infection persists in almost all patients, the pathology of recurrent HCV infection after OLT is not well characterized. To address this issue, we compared the pathological findings of 28 patients who underwent transplantation for HCV-related cirrhosis (group A, aged 47 +/- 15 years; 23 men, 5 women) with those of 21 patients who underwent transplantation for nonviral indications (group B, aged 45 +/- 21 years; 13 men, 8 women) during the first year after transplantation. Patients from group A were assessed for serum HCV RNA by 5' untranslated region nested polymerase chain reaction before and 1 year after OLT. Patients underwent protocol liver biopsies 3 months and 1 year after transplantation. Group A patients more frequently had histological evidence of hepatic steatosis than group B patients, both at 3 months (P = .003) and 1 year (P = .003) after OLT. Fibrosis and portal inflammation were statistically more frequent in group A 1 year after transplantation. The sensitivity of steatosis in detecting histological disease recurrence was 100% at 3 months and 94% at 1 year; the specificity was 40% and 60%, respectively. Conversely, steatosis was 100% specific in detecting viral recurrence, with a sensitivity of 89%. The 1-year actuarial incidence of abnormal transaminase levels was 52% in group A and 13% in group B (P = .05). No biochemical or histological differences between patients infected with genotype 1b and patients with other HCV genotypes were found. Hepatic steatosis is a specific sign of viral recurrence after liver transplantation and a less specific sign of disease recurrence. HCV-infected liver transplant recipients often develop abnormal transaminase levels and liver fibrosis 1 year after OLT; these features are unrelated to HCV genotypes.     

A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States)

To evaluate predictors of contralateral breast cancer risk, we examined data from a nested case-control study of second primary cancers among a cohort of women in western Washington (United States) diagnosed with breast cancer during 1978 through 1990 and identified through a population-based cancer registry. Cases included all women in the cohort who subsequently developed contralateral breast cancer at least six months after the initial diagnosis, but prior to 1992 (n = 234). Controls were sampled randomly from the cohort, matched to cases on age, stage, and year of initial breast cancer diagnosis. Information on potential risk factors for second primary cancer was obtained through medical record abstractions and physician questionnaires. Women who were postmenopausal due to a bilateral oophorectomy (i.e., a surgical menopause) at initial breast cancer diagnosis had a reduction in contralateral breast cancer risk compared with premenopausal women (matched odds ratio [mOR] = 0.25, 95 percent confidence interval [CI] = 0.09-0.68), whereas no reduction in risk was noted among postmenopausal women who had had a natural menopause (mOR = 0.90, CI = 0.39-2.09). Among postmenopausal women, there was a suggestion of a lower risk associated with relatively high parity (2+). A family history of breast cancer was associated with an increased risk (mOR = 1.96, CI = 1.22-5.15) and varied little by menopausal status. Having an initial tumor with a lobular component (c.f. a ductal histology) was not related strongly to risk (mOR = 1.47, CI = 0.79-2.74). The results of the present and earlier studies argue that we have limited ability to predict the occurrence of a contralateral breast tumor. Better predictors will be required before diagnostic and preventive interventions can be targeted to subgroups of patients with unilateral breast cancer.     

A Longitudinal Analysis of the Course of Depressive Symptomatology in Geriatric Patients With Cancer of the Breast, Colon, Lung, or Prostate.

This study mapped the trajectory of depression and its components (depressive mood, somatic expression of depression, and lack of positive affect) for 1 year after an initial cancer diagnosis, revealing the complex nature of the psychological response to the cancer experience. The analysis was based on 4 waves of panel data from 860 older patients with incident breast, colon, lung, or prostate cancer. Predictors of depressive symptoms included cancer site; stage; comorbidities; sociodemographic characteristics; and indicators of physical functioning, symptom severity, and treatment. Patients' overall depressive symptoms declined, especially depressive mood and somatic indicators. By contrast, the sense of well-being did not recover; in fact, it would have deteriorated without improvements in physical functioning and physical symptoms. The present findings show the importance of psychological assessments and symptom management during cancer treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Randomised controlled trial of effects of early discharge after surgery for breast cancer

OBJECTIVE: To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness. DESIGN: Randomised controlled trial comparing discharge two days after surgery (before removal of drain) with standard management (discharge after removal of drain). SETTING: Regional breast unit. SUBJECTS: 100 women with early breast cancer undergoing mastectomy and axillary node clearance (20) or breast conservation surgery (80). MAIN OUTCOME MEASURES: Physical illness (infection, seroma formation, shoulder movement) and psychological illness (checklist of concerns, Rotterdam symptom questionnaire, hospital anxiety and depression scale) preoperatively and at one month and three months postoperatively. RESULTS: Women discharged early had greater shoulder movement (odds ratio 0.28 (95% confidence interval 0.08 to 0.95); P = 0.042) and less wound pain (odds ratio 0.28 (0.10 to 0.79); P = 0.016) three months after surgery compared with women given standard management. One month after surgery scores were significantly lower on the Rotterdam symptom questionnaire in patients who were discharged early (ratio of geometric mean scores 0.73 (0.55 to 0.98) P = 0.035), but rates of psychological illness generally did not differ between groups. CONCLUSIONS: Increased rates of physical or psychological illness did not result from early discharge after surgery for breast cancer. This policy can be recommended for patients with support at home.     

The effects of preoperative therapy with angiotensin-converting enzyme inhibitors on clinical outcome after cardiovascular surgery

PURPOSE: Quality of life of breast cancer survivors 8 years after diagnosis was compared with that among similarly aged women who had never confronted cancer (controls). METHODS: Survivors of a consecutive series of 227 breast cancer patients first treated in 1984 were approached for this study. Random-digit dialing was used to identify controls with the same age and residential distribution as the survivors. Quality of life was assessed in terms of physical health, functional status, psychologic distress, and social functioning. RESULTS: Participation was obtained from 96% (n = 124) of 129 eligible survivors and 61% (n = 262) of 427 potentially eligible controls. Consistently smaller proportions of survivors reported positive quality-of-life outcomes compared with controls, but these differences were generally small and nonsignificant statistically. When limited to women who remained free of disease over the entire follow-up period (n = 98), survivors' quality of life was similar to that among controls, with the exception of arm problems and sexual satisfaction for those women who lived with a partner. In contrast, survivors who developed recurrence or new primary breast cancer (n = 26) experienced a worse quality of life in all domains except social functioning. CONCLUSION: In most domains and for women without further disease events after diagnosis, quality of life does not seem to be permanently and globally impaired by breast cancer. Consequently, breast cancer survivors who remain free of disease probably do not need organized late psychosocial follow-up to improve quality of life. However, arm problems and sexuality are two areas in which additional effort may be still needed to improve quality of life of long-term survivors.     

Is there a basis for prevention of breast cancer with drugs?

The anti-oestrogen drug tamoxifen has led to one of the most important improvements in therapy for breast cancer patients achieved during the last decades. Tamoxifen reduces risk of relapse and improves survival in women with breast cancer. In addition, tamoxifen has favourable effects on the lipoprotein metabolism, reduces morbidity and death from myocardial infarction, and stabilizes bone density in women after menopause. Owing to the good therapeutic results in breast cancer patients and the additional favourable effects of tamoxifen, studies were started among healthy women with elevated risk of breast cancer. The intention was to examine whether tamoxifen could reduce the risk of breast cancer development in healthy women. Recent studies, however, have demonstrated higher risk of endometrium cancer in breast cancer patients treated with tamoxifen, and higher risk of histological abnormalities in the endometrium in healthy women. Prevention trials, when tamoxifen is given to healthy women, are disputed, owing to the apparent carcinogenic effect of tamoxifen.     

Usefulness of CA 15-3 antigen determination for evaluation of response to second-line chemotherapy in patients with breast cancer: preliminary study

The aim of this study was to assess effects of second-line chemotherapy in metastatic breast cancer via determination of CA 15-3 marker. Analysis included 73 women, in whom distant metastases were diagnosed within 14-72 months (median: 43) after the completion of basic therapy. Average age of patients at primary diagnosis was 50.7 +/- 12.6 years. Dominant sites of metastases were: liver (27 patients) and lungs (24 patients). Serum CA 15-3 was examined immunoenzymatically at diagnosis of distant metastases and then after 2-4 cycles (median 4) of anthracycline-based chemotherapy. Changes of mean CA 15-3 values correlated with the UICC response criteria. There was a significant fall in mean levels of CA 15-3 after treatment in patients with complete (p < 0.004) and partial regression of metastatic lesions (p < 0.03). Stabilization and progression of the disease were associated with raise in CA 15-3 mean values, but the difference was significant only in the latter group (p < 0.02). In 31 out of 39 patients (79.5%) with regressive disease (complete and partial response) CA 15-3 levels decreased by at least 25% after treatment. Nine of 11 (81.8%) patients with stable disease had the antigen concentrations that did not vary by more than +/- 25% of the initial CA 15-3 value. CA 15-3 levels raised by at least 25% in 22 out of 23 (95.7%) cases with progressive breast cancer. Overall, CA 15-3 variations correlated with the disease status in 62 (84.9%) patients. These findings confirmed the usefulness of CA 15-3 determinations in evaluating the efficacy of second-line chemotherapy in patients with advanced breast cancer.     

Protective buffering and psychological distress among couples coping with breast cancer: The moderating role of relationship satisfaction.

This study examined whether the association between protective buffering and psychological distress was moderated by relationship satisfaction. Protective buffering is defined as hiding worries, denying concerns, and yielding to one's partner in an effort to avoid disagreement and reduce one's partner's upset and burden. Two hundred thirty-five women diagnosed with early stage breast cancer and their partners completed measures of protective buffering, psychological distress, and relationship satisfaction at 3 time points over an 18-month period after cancer diagnosis. The authors hypothesized that protective buffering would result in more distress among patients and partners reporting higher relationship satisfaction than among patients and partners reporting lower levels of relationship satisfaction. Patients' protective buffering predicted more distress among patients rating their relationships as more satisfactory, whereas the patients' buffering did not predict distress among patients rating their relationships as less satisfactory. Partner relationship satisfaction also moderated the association between patients' buffering and partners' distress. These findings elucidate conditions under which protective buffering may have detrimental effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

MR lesion detection in a breast cancer population

Implementation of MR imaging of the breast as an extension of the existing imaging modalities in the diagnosis of breast cancer was evaluated in a university cancer center, MR imaging of the breast was performed in 54 patients, in whom the MR results were compared with the triple test (the combination of clinical examination, mammographic evaluation, and cytology) and the final histological diagnosis. MR imaging of the breast depicted 30 of the 33 malignancies (sensitivity, 91%). In two of the malignancies, the carcinoma was clinically and mammographically occult. For the three patients with a false-negative MRI diagnosis, the conventional mammography showed suspicions clustered microcalcifications as a sign of in situ carcinoma. For seven patients, MR imaging of the breast incorrectly suggested the presence of a malignant lesion (specificity, 67%). To improve MR specificity, we perform MR-guided ultrasonographic fine-needle aspiration biopsy (FNAB). Although MR imaging of the breast is a highly sensitive examination, conventional x-ray mammography remains the most efficient imaging modality in the diagnosis of breast cancer. In our patient population, MR imaging of the breast had additional value for women with mammographically dense breast tissue and especially for patients with clinical evidence of breast carcinoma that could not be detected with conventional diagnostic methods.     

Psychological and social adjustment to mastectomy: a two-year follow-up study

A consecutive series of 160 women admitted to hospital for breast tumor biopsy was assessed prior to, and at 3, 12, and 24 months following operation for marital, sexual, interpersonal and work adjustment, depression, and personality characteristics by means of rating scales based on structures interviews and standard tests. By 2 years there wery no significant differences in social adjustment between mastectomy patients and benign breast disease controls; 70% of cancer patients were no longer stressed by mastectomy at 1 year. Factors predicting poor adjustment to mastectomy were high preoperative scores on the Hamilton Rating Scale for Depression and the Neuroticism Scale of the Eysenck Personality Inventory; deterioration in sexual adjustment was associated with biological or chronological perimenopausal status. Significantly more cancer than benign disease patients were dissatisfied with the information they received about operation and diagnosis. Implications of these findings for the care of the mastectomy patient are discussed.     

Attenuation of pathogenicity of fowl plague virus by recombination with other influenza A viruses nonpathogenic for fowl: nonexculsive dependence of pathogenicity on hemagglutinin and neuraminidase of the virus

The diagnostic distribution and the relation between diagnosis and symptoms, symptom duration, tumour site, tumour size and breast size were studied in 1 244 women with breast symptoms examined at a special breast tumour clinic. 9% of the women had cancer, 62% fibroadenosis and 6% fibroadenoma. In 18% no breast disease was found. A painful tumour was experienced by 19% of all women with breast cancer, but by 54% of breast cancer patients below 50 years of age. 50% of the patients with fibroadenosis had a painful tumour. This symptom was thus not a discriminating feature between cancer and fibroadenosis in younger women. The reason that most breast tumours, both benign and malignant, are located in the upper outer quadrant is not known. It has been proposed that this might be due to the larger volume of this quadrant as compared with the others. The present results contradict this view.     

Parietal motor syndrome: a clinical description in 32 patients in the acute phase of pure parietal strokes studied prospectively

Although survival rates are useful for monitoring progress in the early detection and treatment of cancer and are of particular interest to patients with new diagnoses, there are limited population-based estimates of long-term survival rates. We used data collected by the Surveillance, Epidemiology, and End Results Program for cases diagnosed during 1974-1991 and followed through 1992 to estimate relative survival at 5, 10, and 15 years after diagnosis of cancer of the breast, prostate, colon and rectum, and lung. Relative survival after diagnosis of breast and prostate cancer continued to decline up through 15 years after diagnosis, whereas survival after diagnosis of lung and colon or rectal cancer remained approximately constant after 5 and 10 years, respectively. Age-specific patterns of survival varied by site, stage, and demographics. Among patients with localized breast and prostate cancer, women who were younger than age 45 at breast cancer diagnosis and men who were 75 years and older at prostate cancer diagnosis had the poorest relative survival. Relative survival among lung cancer patients decreased with age at diagnosis, regardless of stage or demographics, and age-specific patterns of relative survival for patients with cancer of the colon and rectum differed according to race. Among white patients diagnosed with cancers of the colon and rectum, relative survival did not vary by age at diagnosis; among black patients older than 45 at diagnosis, relative survival decreased with age. This study provides population-based estimates of long-term survival and confirms black/white, male/female, and stage- and age-specific differences for the major cancers.     

Randomized trial of breast self-examination in Shanghai: methodology and preliminary results

BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated. PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China. METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer. RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups. CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination. IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination.